Deleting Sensory Circuitry For Heat in Nervous System Causes Hypersensitivity to Cold, Painkiller Side-Effect

Biologists experimentally discovered the surprising phenomenon that deleting the nerve circuitry for heat and some kinds of itch in animals appears to automatically enhance sensitivity to cold in turn. The research results could have implications for people with types of chronic pain, especially regarding a promising but until now problematic new class of painkillers known as TRPV1 antagonists. This drug blocks a neuron receptor protein to turn off pain, but with the major side-effect that many patients shiver and “feel cold” and then go in a state of hyperthermia, an abnormally elevated body temperature.

This phenomenon, which has limited the use of these drugs in patients with chronic pain associated with multiple sclerosis, cancer, and osteoarthritis, could now be explained since TRPV1 is a heat receptor in the primary sensory nerve circuit and blocking it could automatically cause hypersensitivity to coldness in our nervous system.

This new study, published in Neuron, used cell ablation technology to delete the nerve circuit that encodes heat and some forms of itch while preserving the circuitry that sense cold temperatures. This manipulation results in animals that were practically “blind” to heat, meaning they could no longer detect hot temperatures, Zylka explains.

“This discovery has implications for how we perceive hot and cold temperatures and for why people with certain forms of chronic pain, such as neuropathic pain, or pain arising as direct consequence of a nervous system injury or disease, experience heightened responses to cold temperatures,” says Mark J. Zylka, associate professor of cell biology and a member of the University of North Carolina Neuroscience Center.

Zylka’s research sheds new light on how the neural circuits that regulate temperature sensation bring about these responses, and could suggest ways of reducing such side-effects associated with TRPV1 antagonists and related drugs.

Zykla explained that physiological studies indicated that these distinct circuits regulate one another in the spinal cord.

TRPV1 antagonists make patients temporarily blind to heat, which Zylka speculates is analogous to what happened when his lab deleted the animals’ circuit that detects heat: cold hypersensitivity.

Zylka emphasizes that future studies will be needed to confirm that TRPV1 antagonists affect cold responses in a manner similar to what his lab found with nerve circuit deletion.